The ECR Fellowships are specifically for researchers under 40 years of age, who are working in different areas of biological sciences and medicine working in the redox biology field. They are intended to provide ECRs support of up to €10,000 for research or seed-funding for a new project, which should be relevant to the field of redox research and completed within a 12-month period.

Carlos Henriquez-Olguin obtained his Master's Degree in Physiology at the University of Chile, investigating the role of NOX2 on inflammatory signaling in dystrophic muscle cells. He performed a double degree Ph.D. between the University of Chile (Jaimovich E. Lab) and the University of Copenhagen (Jensen TE. Lab), studying the role contribution of subcellular ROS sources during exercise in mouse and human skeletal muscle. Carlos works at the University of Copenhagen, investigating compartmentalized redox signals and skeletal muscle metabolism. He has received several international awards, including the 13th Biochemistry of Exercise Young Investigator Award, the 2022 Catherine Pasquier Award (SFRR-E), and the 2022 Future of Redox Award (SFRR-I).

Insulin resistance is an early stage in the development of type II diabetes and cardiovascular disease. Oxidative stress has been proposed as a unifying factor in the development of multiple forms of insulin resistance. Still, the relative contribution of localized mitochondrial vs. non-mitochondrial is currently unknown. This research project aims to address the knowledge gap regarding the determinants of compartment-specific H2O2 changes, its downstream redox targets, and biological effects in both healthy and insulin-resistant skeletal muscle.
Carlos will pursue a unique combination of metabolic research using state-of-the-art redox imaging biosensors, compartment specific chemogenetic H2O2 generation tools, and advanced redox proteomics to overcome the methodological challenges associated with the study of redox signaling in physiological settings. This study will significantly push state of the art in understanding the determinants of redox signaling and its biological consequences in tissue and compartment-specific context.

Bárbara Rocha is an Assistant Professor at the Faculty of Pharmacy, University of Coimbra (Portugal). She has a BSc in Pharmaceutical Sciences, a MSc degree in Medicine and a PhD in Pharmaceutical Sciences (University of Coimbra). In collaboration with the University of La República (Uruguay) and the Karolinska Institute (Sweden), she studied the biochemical interactions of polyphenols and dietary nitrate in the human stomach, establishing the proof of concept that phenols promote the non-enzymatic production of nitric oxide. She has also shown that pepsin is nitrated and inactivated by dietary nitrate in the stomach and that nitrated pepsin prevents the development of peptic ulcers. Currently, she is studying the impact of nitrate on gut microbiota and microbiota-host redox interactions during antibiotic treatment.

We are not alone. Humans are holobionts where eukaryotic cells live in symbiosis with trillions of microorganisms known as microbiota. Most of these bugs inhabit the gut where they interact with the host through metabolic, immune, neuronal and redox pathways. This crosstalk ensures multiple physiological mechanisms while the disruption of this delicate equilibrium is associated with systemic disorders, ranging from gastrointestinal to neurological diseases. Antibiotics, despite their indisputable pharmacological value, reduce microbiota diversity, metabolic capacity and may be associated with diarrhoea, dyspepsia and severe forms of colitis. Hence, strategies to enrich the microbial flora are necessary to ensure a functional microbiota-host communication during antibiotherapy. In this context, vegetable-based diets, rich in nitrate anion, are now known to produce predictable shifts in bacterial communities with improved metabolic and cardiovascular indicators. The mechanisms underlying such effects include the reduction of nitrate to nitrite and nitric oxide in the gut, other peripheral tissues and the brain. In this proposal, the impact of dietary nitrate on oral and intestinal microbiota will be assessed during dysbiosis. Also, novel methodological approaches will be developed to accurately quantify nitrate and nitrite in biological samples (gut, plasma, brain), a pivotal technological advancement needed for future clinical interventions.

Brandán is a Marie Sklodowska Curie postdoctoral fellow at the KU Leuven Lab for Nanobiology. He is a thiol-based redox biologist who specializes in genetically-encoded fluorescent biosensors, hydrogen peroxide biology and persulfide signalling. He graduated in 2017 from the Vrije Universiteit Brussel with a Ph.D. in bioengineering sciences (Joris Messens' lab), which was followed by a 3.5-year postdoctoral research at the German Cancer Research Center (Tobias P. Dick's lab). His current work focuses on the development of hydrogen peroxide fluorescent biosensors, such as the state-of-the-art HyPer7, with smart photophysical properties for super-resolution microscopy.

Hydrogen peroxide is an oxidant that is endogenously produced by cells and acts as a signalling molecule, with a well-balanced production and delivery being essential for normal cellular and tissue functions. Dysregulation of hydrogen peroxide production compromises such functions and can lead to pathologies: a good example of these is ischemia-reperfusion injury, which generally occurs during heart attacks, strokes, or organ transplantations. This is caused by a prolonged hypoxic period followed by a sudden reoxygenation, which leads to an abrupt increase of oxidant species, including hydrogen peroxide, in mitochondria. The signalling function of hydrogen peroxide was partly unveiled by genetically-encoded fluorescent biosensors, which detect the presence of this compound. However, these biosensors have some limitations: (i) none of them are compatible with super-resolution microscopy, preventing the study of hydrogen peroxide signalling in greater detail; and (ii) most biosensors work in the green spectrum, impeding the analysis of several cellular compartments simultaneously. This project addresses these limitations by designing (i) fluorescent biosensors with photophysical properties compatible with super-resolution microscopy, and (ii) colour-tunable biosensors. The obtained biosensors will then be used to study the detailed fate of hydrogen peroxide in hypoxia-reoxygenation events.

Sarah is a Lecturer in Physiology within the Vascular Biology & Inflammation Section, King’s College London, U.K. Her research seeks to characterize the impact of diabetes and obesity on vascular function. She is particularly interested in how oxidative stress in adverse pregnancy can influence the risk of both mothers and offspring developing cardiometabolic disease in later-life. Using both in vitro and in vivo models, her research explores how induction of the redox-sensitive transcription factor Nuclear Factor Related Factor 2 (Nrf2) using phytochemicals may be protective against adverse outcomes associated with obese, diabetic pregnancy across the life-course.

Increased maternal blood sugar in gestational diabetes (GDM) leads to dysfunction of body cells and organs, due to the over-production of damaging ‘free radicals’ and oxidative damage. GDM increases a mother’s, as well as their child’s, chance of developing Type 2 Diabetes Mellitus (T2DM) and/or cardiovascular disease in later-life. Currently no drugs or lifestyle interventions can completely reverse GDM or prevent risk of later-life disease. Sarah has established a model of obesediabetic pregnancy in mice, mimicking GDM. Her findings show a broccoli extract, sulforaphane (SFN), helps reduce diabetic symptoms in mouse mothers and their offspring, but the underlying mechanism(s) remain largely unknown. The pancreas produces insulin, a hormone important for regulation of blood sugar. In pregnancy the pancreas undergoes major adaptation, but due to its high energy requirements and low levels of protective antioxidants, its highly sensitive to radical production and oxidative damage. This project will help us understand if/how SFN protects the maternal pancreas during pregnancy by studying its effects on: (i) islet mitochondrial function, oxidative stress and the potential protective role of inducible Nrf2 antioxidant defences and (ii) the potential for attenuation of maternal islet oxidative stress to improve maternal glucose control.

Eduardo Fuentes-Lemus graduated as a Pharmacist from the Pontifical Catholic University of Chile (2014) and received his PhD in Chemistry in 2018. He has been a Postdoc in the Department of Biomedical Sciences (University of Copenhagen) since 2020 after receiving an Individual Fellowship under the programme Horizon 2020 (European Commission, Marie Skłodowska-Curie Actions). His current research interests include understanding different physico chemical aspects that modulate protein oxidation and glycation, particularly the effect that biological interfaces, crowding and microdomains would have on the pathways and kinetics of protein modification.

Amyloidoses (e.g. tauopathies and synucleinopathies) including Alzheimer’s and Parkinson’s diseases are a major health, economic and social problem. These diseases have a multifactorial aetiology with oxidative stress and protein oxidation being major risk factors. Oxidation is known to lead to protein aggregation, a major hallmark of amyloidosis. Emerging evidence suggests that macromolecular crowding, a common feature of cells that arises from the presence of high concentration of molecules, can alter the extent of protein oxidation (and therefore probably aggregation), but this is poorly supported experimentally. Crowding favours protein self-assembly, which triggers liquid-liquid phase separation, another key driver of amyloidosis. Eduardo will examine the hypothesis that macromolecular crowding and liquid-liquid phase separation play a central role in modulating the rate and extent of protein oxidation and aggregation, and therefore disease development. To test this hypothesis, he will investigate whether the nature and concentration of molecules that contribute to crowding, affect the pathways and time-course of reactions that lead to protein oxidation in dilute versus crowded solutions. He will subsequently investigate the effects of crowding on the aggregation of native and oxidized alpha synuclein, a process observed commonly observed in Parkinson’s disease. This project will therefore elucidate pathways that contribute to protein aggregation in vivo.